ES2843026T3 - A method of calculating or approximating a value representing relative blood volume, and devices - Google Patents

Abstract

A blood treatment device for treating a patient by dialysis, comprising at least one controller, configured to control the device according to a computer-implemented method, to calculate a value representing a recharge volume (V recharge) of a patient, which can be observed or found during or due to a patient's blood treatment, where a target range of the relative blood volume (RSV_final) to be achieved by blood treatment at the end of a treatment session is established based on a recharge volume (V recharge) of the patient; where the recharge volume (V recharge) is obtained by the following equation ** (See formula) ** or V_recharge = a * VUF / Hb + b * SH + c where the relative blood volume (VSR_final) is obtained at starting from the following equation ** (See formula) ** or by ** (See formula) ** where: "a", "b", "c", "d" are parameters; Hb_initial represents the hemoglobin concentration at the beginning of a blood treatment session; Hb is the concentration of hemoglobin; V_recharge represents the recharge volume; VUF represents the ultrafiltration volume; IUF represents the ultrafiltration index; SH represents overhydration of the patient, for example, at the beginning of a blood treatment session; TMJ represents the fat mass of the patient in question; LTM represents the muscle mass of the patient in question; K_Guyton represents the Guyton factor; and Vs_initial represents the absolute blood volume of the patient at the beginning of the treatment session.

Description

DESCRIPTION

A method of calculating or approximating a value representing relative blood volume, and devices

The present invention relates to a blood treatment device according to claim 1.

During extracorporeal blood treatment, there is a decrease in the patient's blood volume (VS) and, therefore, in the patient's relative blood volume (RSV). This decrease depends on a series of parameters, such as the absolute blood volume (SV) at the beginning of the treatment, the ultrafiltration index (IUF) applied, if it is applied, and the like. Patients who are treated with an ultrafiltration index (IUF) set (too) high are likely to suffer syncope during, for example, dialysis, due to the amount of fluid removed from their body by the treatment. Patients treated with an ultrafiltration index (IUF) set as (too) low are likely to spend unnecessary time at the treatment site (hospital, clinic or even at home, connected to the treatment machine), or worse, than are sent home again without reducing their overhydration level (SH) by the appropriate amount.

From document US 7,801,598 B2 a device and a method for the determination of dry weight are known, by means of the continuous measurement of the resistance and the calculation of the circumference in a body segment through the analysis of segmental bioimpedance.

From US 2006/226079 A1 a hemodialysis apparatus and a method for hemodialysis are known. From US 7,170,591 B2 a blood treatment device and a blood treatment method are known.

From US 5,938,938 A an automatic dialysis method and apparatus are known.

From US 7,788,038 B2 an information control system of a blood treatment device and biological information, a blood treatment device information control device and biological information, and a method of control information of the blood treatment device and biological information.

From WO 2006/002656 A1 a method and a device are known for determining the hydration and / or nutritional status of a patient.

From US 7,785,463 B2 an extracorporeal renal replacement modeling system is known. In the article "Assessment o f refill and hypovolaemia by continuous surveillance o f blood volume and extracellular fluid volume" by HJ Bogaard et al., Nephrology Dialysis Transplantation, Oxford University Press; 9: 1283-1287, the hypovolemia due to ultrafiltration during renal replacement therapy is discussed.

In the article "Importance o f Whole-Body Bioimpedance Spectroscopy for the Management o f Fluid Balance" by Peter Wabel et al., Blood Purification 2009; 27: 75-80, the treatment of chronic volume overloads in patients is discussed.

In the article "Bioimpedance Analysis in Dialysis: State of the Art and What We Can Expect" by James Tattersall, Blood Purification 2009; 27: 70-74, the removal of fluids using dialysis is discussed.

Thanks to the present invention, a blood treatment device is suggested for treating a patient according to a method to calculate or approximate a value representing the relative blood volume (RSV) at a given time.

The patient can be a human or an animal. The patient can be healthy or sick. The patient may or may not need medical attention.

The blood treatment device according to the present invention is defined by the combination of features of claim 1. Accordingly, in one aspect of the present invention, the blood treatment device comprises at least one apparatus disclosed below, being o the apparatus comprising a controller.

Embodiments may include one or more of the following features.

In certain embodiments in accordance with the present invention, the moment is within a session blood treatment in particular. In some embodiments, the time is a time when a blood treatment session has just ended.

In some embodiments according to the present invention, "observing" or "finding" a value is to be understood as measuring the value, calculating the value, or obtaining or determining it from other values of other parameters that influence the value in question.

In certain embodiments according to the present invention, a measured, observed, calculated or determined value "due to blood treatment" means the value of a parameter that has been modified due to blood treatment. The value itself can be measured, observed, calculated or determined during, before or after a blood treatment session.

In some embodiments according to the present invention, the blood treatment can be a hemofiltration, an ultrafiltration and / or hemodialysis method.

In certain embodiments according to the present invention, "considering" a value means taking the value into account, in particular, in a subsequent mathematical calculation. This can occur with a mathematical formula that refers to or understands the value considered, or by establishing a mathematical relationship between certain parameters or the value that includes the "considered". In some embodiments according to the present invention, "considering" a value can be understood as using the value as an input value that is input, for example, into a (mathematical) formula, a computer, a control unit, a processor. , or another similar. The input value can come from a measurement, a diagram, a spreadsheet, a table, or something similar, for example.

In some embodiments in accordance with the present invention, a value that represents or reflects a parameter, such as absolute blood volume or the level of overhydration of a patient, means a value that directly or indirectly expresses or indicates that parameter. For example, in certain embodiments according to the present invention, a value that represents or reflects the overhydration of a patient can be "3" followed by the dimension "liters", while a value that indirectly allows to obtain or determine or approximate the Overhydration of the patient can also be "3" in the dimension "kilograms", or it can be the abdominal perimeter, for example.

In some embodiments according to the present invention, a value that represents or reflects a parameter such as absolute blood volume, relative blood volume, recharge volume, or overhydration of the patient is to be understood as absolute blood volume, relative blood volume , the refill volume or overhydration or as values of these, for example, indicated in "liters".

In certain embodiments in accordance with the present invention, a "level" of overhydration can be understood as the extent or extent of overhydration. Both the term "overhydration" and the term "level of overhydration" can be related to absolute or relative values. If understood as a relative value, "overhydration" may be related to the normohydrated state of the patient, who does not need fluid extraction and / or whose kidneys function like those of a healthy person.

In some embodiments according to the present invention, the level of overhydration or overhydration is defined as the difference between the weight of the patient who needs to remove excess water due to kidney problems and the dry weight of the patient. Dry weight can be the weight of the patient in a condition where there is no excess fluid or where excess fluid does not have to be removed. The dry weight of the patient can be defined as in WO 2006/002685 to 1. The respective disclosure of WO 2006/002685 A1 is hereby incorporated by reference.

In certain embodiments in accordance with the present invention, overhydration and overhydration level (these terms may be used interchangeably in some embodiments in accordance with the present invention) refer to an overhydration value or the overhydration of the patient just before starting. the blood treatment session, at the start of the blood treatment session or during the blood treatment session.

In some embodiments according to the present invention, overhydration or the level of overhydration of a patient means the water or excess fluid accumulated within the body that the skilled person understands as fluid that must be removed (in part or in whole) by blood treatment.

In certain embodiments in accordance with the present invention, the overhydration or the level of overhydration is equal to the water or excess fluid accumulated within the body that the kidneys would have removed from the body if they were functioning properly.

In some embodiments according to the present invention, some or all of the method steps are carried out by means of corresponding devices, such as one or more processors. The devices are adapted and / or configured to carry out the respective steps of the method.

The method carried out by the controller is a computer-implemented method.

In some embodiments according to the invention, the method is an automated dialysis method.

In some embodiments in accordance with the present invention, the disclosed method is an operator-independent method for calculating or approximating or predicting a value representing absolute blood volume, relative blood volume, or refill volume, or for controlling a monitoring device. blood treatment.

In certain embodiments, the method encompasses considering the absolute initial blood volume at or before starting blood treatment, in order to calculate or approximate or predict either a value representing the relative blood volume or a value representing the recharge volume. .

In some embodiments, to evaluate the absolute initial blood volume, at least one value reflecting lean mass and at least one value reflecting the patient's body fat mass, and / or approximations thereof, are considered.

In certain embodiments of the present invention, the recharge volume (V recharge) is obtained by the following equation (also treated as equation (7) below):

I U F

^{V _ [reload = a * VUF b *} - ---------- ^{+ C * SH d}

H b _ in ic ia l

In this equation, VUF, IUF, and SH represent ultrafiltration volume, ultrafiltration index, and overhydration level, as used herein. "Hbjnicial" is the concentration of hemoglobin in blood or any other suitable body fluid or tissue before or at the start of the treatment session, for example immediately after the start of treatment.

In certain embodiments according to the present invention, the parameter "a" is equal to 0.6015, "b" is equal to 0.0097, "c" is equal to 0.0223, and "d" is equal to 0, 0442.

In some embodiments according to the present invention, one or more of "a", "b", "c" and "d" can be a negative value. In certain embodiments in accordance with the present invention, one or more of "a", "b", "c" and "d" may be equal to zero.

Although the values indicated above for "a", "b", "c" and "d" have been useful to the inventors of the present invention, the use of the above equation, of course, is not limited to it. In fact, the deviation of the chosen values for "a", "b", "c" and / or "d" is possible and is contemplated.

Obviously, the equation given above can also be expressed differently. Obviously, it can also have another structure, such as V_reload = a * VUF / Hb + b * SH + ... or similar ones.

In some embodiments, the added or added recharge volume can be calculated or approximated during the entire treatment session. In certain embodiments, the refill volume values can be calculated or approximated at certain times. In the latter case, the recharge volume values of interest can be obtained from, for example, an exponential or exponential extrapolation or intrapolation.

In some embodiments according to the present invention, a final relative blood volume value is predicted to arrive at the end of a blood treatment session without causing intradialytic pathological complications, such as hypotonic episodes, seizures, syncope, seizures, vomiting, dizziness, nausea. or similar.

A hypotonic episode or seizure, in certain embodiments of the present invention, is defined as the ailment that the patient feels subjectively, related to low blood pressure or a drop in blood pressure that occurs more or less suddenly.

In some embodiments in accordance with the present invention, a hypotonic episode, seizure or syncope, is defined as a drop in blood pressure that exceeds a decrease of, for example, 30 mmHg in systolic blood pressure measured before or at the beginning of the treatment session (or other defined or predefined decrease in mmHg).

In certain embodiments in accordance with the present invention, a hypotonic episode, seizure, or syncope, is defined as an episode in the patient that requires medical assistance, such as causing the patient to assume a different posture, stopping ultrafiltration, or delivering an infusion of, for example, NaCl or the like.

In certain embodiments of the present invention, the method encompasses the step of controlling a recording apparatus blood treatment as a function of the relative blood volume calculated or approximated by means of the method according to the present invention. Similarly, in some embodiments of the present invention, the method encompasses the step of controlling a blood treatment apparatus as a function of the final value of the relative blood volume calculated or approximated or predicted by means of the method according to the present invention.

In certain embodiments of the present invention, the method encompasses the step of calculating or optimizing the duration of treatment or the length of time a certain future blood treatment session lasts. The calculation or optimization is carried out taking into account the relative blood volume or the final value of the relative blood volume that is obtained with the method according to the present invention.

In some embodiments according to the present invention, the method encompasses the step of correcting the relative blood volume by means of the patient's overhydration level (or considering the same) to be a normalized or normohydrated relative blood volume (normohyd RSV).

The method comprises the step of determining a target range of the relative blood volume to be achieved with the blood treatment at the end of a treatment session.

In many embodiments of the present invention, the apparatus comprises corresponding devices, such as one or more processors, to carry out the disclosed method. The devices are adapted and / or configured to carry out the respective steps of the method.

In certain embodiments of the present invention, the apparatus is or comprises a monitor.

In some embodiments of the present invention, the apparatus is configured to carry out the method in accordance with any aspect disclosed herein.

In certain embodiments of the present invention, the apparatus comprises an output device for outputting the results provided by carrying out the respective method.

In some embodiments of the present invention, the apparatus is configured to control a device for treating a patient's blood with respect to a target value or range representing the relative blood volume calculated or approximated or predicted by a method described herein. .

In certain embodiments, the control is such that the treatment session is terminated or interrupted (or the ultrafiltration index (IUF) is adjusted so that the absolute blood volume or relative blood volume (RSV) does not fall below a value. determined or predetermined) once an approximate or calculated value or the target range representing the relative blood volume is achieved or reached, thanks to the treatment.

In some embodiments of the present invention, the apparatus is configured to control a device for treating a patient's blood, such that the treatment session is over or interrupted once a final value of relative blood volume is measured or calculated that it has been predicted as the final value or target range of the relative blood volume. This can be a final value or target range of the relative blood volume that has been achieved or reached without the patient suffering any hypotonic episode.

The device according to the present invention is intended to treat a patient by dialysis.

In some embodiments according to the present invention, the device for treating a patient is a hemofiltration, ultrafiltration and / or hemodialysis treatment machine.

In certain embodiments of the present invention, the apparatus is configured to control a device for treating the blood of a patient, such that the treatment session ends or is interrupted once a threshold or predetermined value of the absolute blood volume of the patient.

In some embodiments according to the present invention, the patient's absolute blood volume is determined during the blood treatment session taking into account the relative blood volume determined during the blood treatment session.

In certain embodiments in accordance with the present invention, the level of overhydration is approximated, calculated or defined based on measured values and / or calculations reflecting overhydration or relative overhydration (SHrel: overhydration (SH) relative to extracellular water (AEC)), etc. of the patient. With regard to a definition of overhydration, as used in certain embodiments of the present invention, reference is made to WO 2006/002685 A1, where SH equals a * AEC + b * AIC + c * body weight. The respective disclosure of WO 2006/002685 A1 is hereby incorporated by reference. It should be understood that the Overhydration can be determined in a number of ways, all of which are known to those skilled in the art. One such method involves measuring a dilution and calculating overhydration based on it.

In some embodiments in accordance with the present invention, the patient's level of overhydration can be expressed by age-corrected overhydration or relative overhydration (SHEDrel). In doing so, certain effects, for example due to age, can be eliminated to achieve more relevant values.

In some embodiments according to the present invention, the patient's overhydration level is expressed in a single value, in particular, a value with the dimension of "liters".

In certain embodiments in accordance with the present invention, the level of overhydration is measured or approximated prior to dialysis or as a function of the patient's pre-dialysis values.

In some embodiments in accordance with the present invention, the pre-dialysis (pre-Dx) values or calculations may be data obtained immediately, that is, moments or minutes before starting the next dialysis treatment. However, the present invention is not limited to this. The data can also be obtained at any other time. Pre-Dx data appears to be more stable than others. Therefore, using them can be advantageous.

In certain embodiments in accordance with the present invention, a target range is defined on a diagram representing both relative blood volume and time. The target range can alternatively be a target area. Also alternatively, the diagram can be a graph. The diagram can be a Cartesian coordinate system, also called a "rectangular coordinate system."

To determine the level of hydration or overhydration, any appropriate monitor can also be used, such as bioimpedance-based monitors or dilution techniques.

The monitor for obtaining data related to the state of hydration or the level of overhydration can be a monitor as described in WO 2006/002685 A1. The respective description of WO 2006/002685 A1 is incorporated into the present application by way of reference. Obviously, the present invention should not be understood to be limited to monitors that determine the hydration status of the patient by bioimpedance measurements, as described in WO 2006/002685 A1. Other methods known in the art, such as dilution measurements, as well as any other method known to those skilled in the art, are also contemplated and encompassed by the present invention.

In some embodiments, the apparatus further comprises an output device for outputting the results provided by the apparatus. The output device can be a monitor with a screen, a plotter, a printer, or any other means that provides data output.

In certain embodiments, the hemoglobin (Hb) level, mass, or concentration of the patient is calculated and / or measured. Measurement and calculations can be performed by any method known in the art, using any suitable device for this. In particular, in some embodiments, the respective data can be obtained by measuring the concentration or mass of hemoglobin from samples of blood and / or blood contained in extracorporeal blood lines by means of an appropriate monitor. Measurements can be performed by measuring the optical properties of the blood with optical sensors and / or evaluating the acoustic properties, such as transit times and / or propagation velocities of the ultrasonic pulses, with ultrasonic sensors.

In certain embodiments, the apparatus comprises a monitor for measuring hemoglobin (Hb) concentrations (eg, in [g / dl]) and / or for determining blood volume by means of any monitor, as described in "Replacement of Renal Function by Dialysis "by Drukker, Parson and Maher, Kluwer Academic Publisher, 5th Edition, 2004, Dordrecht, The Netherlands, at pages 397-401 (" Hemodialysis machines and monitors "), the respective description of which is hereby incorporated herein. reference mode.

In some embodiments, the monitor is configured to measure blood volume and / or hemoglobin concentration through the measurement of electrical conductivity.

In certain embodiments, the monitor is configured to measure blood volume and / or hemoglobin concentration through optical density measurement.

In some embodiments, the apparatus is configured to measure blood volume and / or hemoglobin concentration through viscosity measurement.

In certain embodiments, the apparatus is configured to measure blood volume and / or hemoglobin concentration through density measurement.

In some embodiments, the apparatus comprises one or more corresponding probes and / or one or more sensors to carry out the measurements, such as electrical conductivity sensors, optical sensors, viscosity sensors, density sensors, and the like.

In specific embodiments, the device can be used to treat a patient (or the patient's blood) by hemofiltration, ultrafiltration, hemodialysis, etc.

The embodiments can provide one or more of the following advantages.

Thanks to the present invention, before or at the beginning of the treatment session (for example, if it is necessary to know the initial or initial Hb concentration, a value that can be obtained only (shortly after) having started the treatment), A final relative blood volume value can be determined that the patient is likely to tolerate without severe drops in blood pressure, blood pressure crisis, or syncope (the latter is also referred to as a pathologic complication in this document).

This can provide the possibility to control the dialysis machine according to a reliable prediction (RSV). Accordingly, the relative (critical) blood volume calculated or predicted in advance can advantageously be used as a target value for the relative blood volume. Consequently, the dialysis machine can be controlled. For example, the machine can be programmed to stop ultrafiltration once the calculated or predicted relative (critical) blood volume has been determined or reached, or to adjust the IUF such that the target RSV is not insufficient.

Furthermore, in certain embodiments, the time or duration of dialysis can be advantageously optimized in certain embodiments of the present invention, since being aware in advance of the anticipated relative blood volume, which the particular patient will most likely tolerate, allows control of the machine. dialysis so that the intended relative blood volume is achieved as quickly as circumstances require.

Also, once the predicted relative blood volume is reached in advance, the dialysis procedure can be stopped, as it may appear that no further ultrafiltration is needed or recommended.

Furthermore, to optimize dialysis time, the control described herein ensures, in certain embodiments, that the predetermined ultrafiltration volume is removed from the patient in a minimum or optimal time.

Furthermore, the ultrafiltration index can be established once the duration of dialysis has been established and the relative blood volume or the critical relative blood volume has been predicted or calculated by means of the present invention. The ultrafiltration rate determined in this way will not cause a serious drop in blood pressure (seizure, syncope, or the like).

Another advantage may be that the individual refill properties of the patient in question can be evaluated when the specific refill volume is known. The refill volume can be calculated as described above with respect to the present invention. An evaluation of the individual refill volume can help to discover certain diseases or defects of the patient with respect to the conditions of his capillaries (for example, the presence of a capillary leak syndrome); It may be helpful to check osmotic pressure (albumin concentration) and other factors. Likewise, the evaluation of the individual refill volume may allow to provide a more individual dialysis treatment. For example, the duration of dialysis (which at least in part can be derived from the refill volume) can be tailored to the particular needs of the patient. Either way, knowing the specifics of the patient's refill volume can help to further tailor the treatment to the particular needs of the patient.

In addition, through the proper use of the equations shown above, the expected level of overhydration can be estimated for the beginning of the next treatment session.

Accordingly, the disclosed method and apparatus, and other devices such as the blood treatment device according to the present invention, can advantageously solve the technical problem, which is: how to automatically stop an automatic blood treatment before the patient starts suffer or feel uncomfortable. Another technical problem that can be advantageously solved by the present invention is how to shorten the time it takes for the blood treatment apparatus to treat the patient while achieving the intended or requested removal of excess fluid (or overhydration).

Other aspects, features, and advantages will be apparent from the description, figures, and claims.

Figure 1 shows the drop in relative blood volume per liter of ultrafiltration volume during dialysis with respect to initial overhydration (in liters);

Figure 2 shows data including those already used for the figure of figure 1 in another classified presentation; Figure 3 shows a relationship between refill volume as predicted versus a refill volume reference;

Figure 4 shows the agreement between the predicted relative blood volume and the actually measured relative blood volume at the end of the treatment;

Figure 5 shows the relative blood volume measured over the course of a single treatment session; Figure 6 shows another way of controlling a blood treatment machine in accordance with certain embodiments of the present invention;

Figure 7 shows another way of controlling a blood treatment machine in accordance with certain embodiments of the present invention;

Figure 8 shows another way of controlling a blood treatment machine in accordance with certain embodiments of the present invention;

Figure 9 shows the relative blood volume normohydrated with respect to overhydration;

Figure 10 shows a first apparatus comprising a controller for carrying out the disclosed method; and Figure 11 shows a second apparatus comprising a controller for carrying out the disclosed method. Figure 1 shows the correlation between the drop in relative blood volume per liter of ultrafiltration fluid in percent (summary:% AVSR / VUF, the VUF measured in liters [l]) during dialysis and initial overhydration (in liters). The data in Figure 1 has been collected from several patients treated by ultrafiltration.

As can be seen in Figure 1, the drop in relative blood volume per liter of ultrafiltration fluid is less the greater the overhydration before dialysis ("pre-Dx" overhydration).

Figure 2 shows data including those already used for the Figure 1 graph plus additional measurement data. Another difference between figure 1 and figure 2 is the different way of representing the available data. In Figure 2, patients have been classified as having started dialysis with SH overhydration of less than one liter or more than one liter.

As can be seen in both figure 1 and figure 2, the drop in relative blood volume per liter of ultrafiltration fluid (summary:% AVSR / VUF [l]) is less in patients (24 patients) who started dialysis with increased overhydration, and vice versa. Furthermore, as in Figure 1, Figure 2 only shows the data that have been observed in patients who have had more than 1.3 liters of ultrafiltration fluid removed (VUF> 1.3 liters). As can also be seen in figure 1 and figure 2, to determine a target VSR value to be reached at the end of the treatment session, or to determine an optimized or critical VSR value (VSR_critical or VSR_min_tolerated), obviously, the level of overhydration is important information and should therefore be taken into account when establishing an optimal individual and critical RSV or a minimum tolerated RSV.

The representations in Figure 1 and Figure 2 can help to understand why certain patients experience significant or severe drops in blood pressure (hypotensive episode or seizure) during dialysis with different relative blood volume values, while others do not. One reason may be the improved recharge (due to the greater amount of water comprised within the interstices) in overhydrated patients; another reason may be the increase in absolute blood volume.

Likewise, Figures 1 and 2 help to understand why a particular patient may suffer a syncope when a certain level or value of relative blood volume is reached during a first dialysis session, but does not suffer another syncope when it is reached. relative blood volume during another second dialysis session. Hereinafter, by way of example, an approach that reflects this relevance of overhydration before dialysis and its origin (VSA being the general drop or change in absolute blood volume during dialysis) are explained:

(1) 75 A - ^{VSJ inal - V S_in ic ia l - VUF V_r echarge}

(2) ^{V recharge = VS _ end al - VS jn ic ia i VUF}

VS_inicial is equal to the normalized VS_0 plus the part of the excess fluid present in the blood compartment:

Assuming that VS_0 is equal to 0.1 * LTM + 0.01 * ATM, where LTM is the muscle mass and ATM the fat mass of the patient in question, the recharge volume can be expressed as follows:

0,01

(5)

0.01

Solving (5) for the VSR_final:

100(6)

100

In any equation presented in the present description, VUF means ultrafiltration volume, SH means overhydration before starting dialysis.

V_recharge can be estimated, as an example, as follows:

(7) V ^recharge = a * VUF b * ^{- R} ^ C * SH d

H O_initial

As noted above, in certain embodiments according to the present invention, the parameter "a" is equal to 0.6015, "b" is equal to 0.0097, "c" is equal to 0.0223, and "d" is equal to 0.0442. However, this should not be understood as limiting. Any other estimate is also contemplated.

The values indicated above for the parameters "a", "b", "c" and "d" have been found empirically. They have been analyzed step by step to determine their importance and have been cross-validated.

Of course, other approaches to estimating recharge volume based on VUF, IUF and SH are also contemplated. In those alternative approaches, the initial Hb may be included. However, it is not required.

Likewise, the duration of the dialysis session T_dialysis can be calculated by dividing VUF by IUF.

Furthermore, SH overhydration can be expressed by a function f (VUF, IUF, LTM, ATM, Hb_initial, K Guyton, VSR_final). The duration of the dialysis session T_dialysis can be expressed by a function f (VUF, SH, Hb_initial, LTM, ATM, K Guyton, VSR_final). The ultrafiltration index IUF can be expressed by a function f (VUF, SH, Hb_initial, LTM, ATM, K_Guyton, VSR_final, T_dialysis).

Figure 3 illustrates the relationship between the refill volume (Vol_recharge_ref in liters) as predicted by equation (5) with respect to a refill volume reference (Vol_recharge_ref in liters). These reference values were calculated for the treatments illustrated by equation (5) and are plotted along the x-axis, while the values found by equation (7) are plotted along the y-axis.

In the embodiment corresponding to Figure 3, it is believed that the expansion of blood volume is proportional to the overhydration Sh due to a constant value of K_Guyton and that LTM, ATM, etc. have been determined to be correct enough.

As can be seen in Figure 3, the predicted recharge volume (Vol_recharge_ref in liters) corresponds quite well to the reference of the actually observed recharge volume (Vol_recharge_ref in liters).

Similarly, what has been demonstrated above with reference to figure 3 can also be seen in figure 4. The data represented in figure 4 show that the predicted relative blood volume RSV_prev [in%] corresponds very well to the relative blood volume achieved. (RSV_final_reached [in%] by eliminating the ultrafiltration volume established by the doctor from the blood before starting treatment.

The standard deviation (SD) of the displayed values is 1-2.2%. Each point shown in Figure 4 represents a complete treatment session (in total, 109 measurements).

It is observed that the data shown in the figures discussed here were obtained during or by means of treatments that were carried out with a constant ultrafiltration index applied. However, it is contemplated that the idea of the present invention can also be realized with ultrafiltration rates that do not remain constant during treatment.

Figure 5 represents the measured relative blood volume (RSV_measured in [%]) over the course of a single treatment session. Relative blood volume (RSV) is illustrated over the duration of the session (time t in minutes).

The reference sign VSR_med represents the actual measured course of relative blood volume over time t. The reference sign VSR_prev shows the predicted relative blood volume. As can be seen, there is hardly any deviation (the deviation is represented by the arrow in Figure 5) between the predicted relative blood volume and the actual end. In any case, controlling the dialysis apparatus as a function of the relative blood volume calculated or predicted in advance VSR_prev would not have caused any hypotensive crisis with respect to the particular treatment session reflected in figure 5.

FIG. 6 through FIG. 8 are intended to explain additional ways of how to control a blood treatment machine in accordance with certain embodiments of the present invention. From Figure 6 to Figure 8, the course of the relative blood volume RSV is illustrated during time t [min]. Data were recorded during three different dialysis treatments for patient "46249", who had an absolute, normohydrated and constant initial blood volume VS_0 of 4.7 liters at the start of each treatment session. The patient's SH overhydration was different: 1.4 (figure 6) and 2.3 liters (figure 7). In these three sessions, an ultrafiltration volume between 1.5 (figure 6) and 2.3 liters [l] (figure 8) was removed, respectively.

In each of Figures 6-8, the RSV_above diagram shows the evolution of the relative blood volume during the time elapsed since the start of treatment. With respect to the present invention, the term RSV_above reflects the results of a blood volume monitor measurement as has been done to date in the prior art. The expression RSV_previous (which could therefore also be called RSV_classic or RSV_standard or something similar, and which is calculated as VS (t) / VS_initial) shows the measured relative blood volume. However, RSV_anterior is not a normal hydrated blood volume. As can be seen from Figures 6-8, the treatment begins with a relative blood volume RSV_anterior of 100% and ends with a relative blood volume reduced between 85% and 95%. Therefore, as can be easily understood from these figures, the relative blood volume measured at the end of the treatment may differ from treatment to treatment, although the same amount of fluid was reduced in each treatment, because the relative blood volume was determined with respect to different absolute values of blood volume at the beginning of treatment. For this reason, controlling a dialysis machine (or appropriately setting the ultrafiltration rate or volume) based on a set or predetermined critical or final relative blood volume value can be difficult in the prior art with certain patients (a difference from what can be achieved with the means of the present invention).

In accordance with some embodiments of the present invention, the RSV_normohid relative blood volume (also referred to herein as "normohydrated relative blood volume") is "corrected" for overhydration found in the patient in question prior to using the dialysis session to monitor the dialysis machine.

The normohydrated relative blood volume VSR_normohid can be calculated, for example, as follows:

/ q \ I / CD /> \ ^wcn / j. \> _{(8) vo K normoh id \ TJ =} ^{v ¿_absolute_dialysisstart,} _{* vo K previous \ TJ ~} ___ ^{^ _} - ^G - ^uy - ^C - ^o - ^{n \ / CD} / _{* vo K prev io r \ TJ}

where VS_absolute_inicioDialysis represents the absolute blood volume at the beginning of the treatment session, and where VS_0 represents the absolute blood volume corrected for the contribution of fluid to the vessel system due to overhydration. The Guyton factor K_Guyton indicates how much of the overhydration is comprised within the vessel system.

Thus, an overhydrated patient would begin his dialysis treatment with a relative normohydrated VSR_normohid blood volume greater than 100%, as can be seen in Figures 6-8. In the example of Figure 6, the patient started treatment with a 1.4 liter overhydration. 1.5 liters were removed. The actual blood volume VS_absolute_inicioDialysis was 4.7 liters plus 1.4 / 3, equal to 5.2 liters. The normohydrated absolute initial blood volume VS_0 was 4.7 liters. The Guyton factor K_Gyton, which indicates how much of the overhydration is comprised within the vessel system, was assumed to be 3. Therefore, the patient started with a Fictitious relative blood volume or a normohydrated relative blood volume of 110% (5.2 liters / 4.7 liters) at the dialysis session. At the end of dialysis, the normohydrated relative blood volume RSV_normohid was 100%. By then, the absolute blood volume of 4.7 liters had been restored and the overhydration had been reduced to 0 liters. Taking into account that the VUF ultrafiltration volume was 1.5 liters in the present treatment, the patient's recharge volume was 4.7 liters less (5.2 less 1.5 liters), equal to 1 liter.

As is easily understood from Figures 6-8, controlling dialysis based on RSV_normohid normohydrate relative blood volume is fairly straightforward, as it is sufficient to stop ultrafiltration once a RSV_normohid relative blood volume of 100 is reached. % in the respective treatment session, assuming no recharging is performed after dialysis. This can be achieved by running a very low IUF at the end of the treatment, so that the vascular and interstitial spaces are more or less close to equilibrium (in terms of filtration pressures). As is also obvious from the above, the 100% stop value can remain unaltered for the normohydrated relative blood volume RSV_normohid, both in each individual treatment and regardless of the particular patient being treated. Controlling the machine as proposed herein can reduce programming effort.

Figure 7 reflects another treatment of the same patient. Due to the higher SH overhydration of 2.3 liters (compared to the treatment in figure 6 where it was 1.4 liters), the dialysis in figure 7 starts with a relative normohydrated relative blood volume RSV_normohid of 117% (compared with 112% of figure 6).

Additionally, as indicated in Figure 8, it may be contemplated to establish a target RO range for the relative normohydrated blood volume RSV_normohid to be achieved at the end of the treatment.

For example, the RO target range can be set 3%, 5% or more below and / or above the expected 100%.

Furthermore, the RO target range does not necessarily encompass the final value of the normohydrated relative blood volume VSR_normohid, which is always 100%. The range can also be used to encompass an area around any desired end value for the treatment in question. Therefore, under certain circumstances, a target range refers to a final value of, for example, 90% or 95%, depending on the patient.

Figure 9 shows the relative blood volume normohydrate VSR_normohid plotted with respect to overhydration SH. Furthermore, in FIG. 9, a starting point Dx_initial and an end point Dx_final are illustrated for the dialysis treatment in question. An RO target range is established which indicates an area in the graph of Figure 9 that is acceptable for the values of both the normohydrated relative blood volume RSV_normohid, and the overhydration Sh at the end of the treatment.

It is noted that instead of SH, as described above, a time-averaged value of SH (TAFO, a mean between the values before and after overhydration) can be used to incorporate the idea of the present invention, including the idea described with respect to Figure 9 without being limited thereto.

In figure 9, two possible ways of treatment or control of the dialysis machine are represented as C1 and C2.

At the C2 end point, the patient has a normohydrated blood volume VS; however, the patient is still overhydrated. Consequently, a surge of water from the interstices into the blood vessels should be expected, as the C2 end point will continue to rise in the illustration in Figure 9 after treatment (SH will remain at a constant level, but blood volume VS will increase).

On the other hand, at the end point C1 there is no rebound because the patient is not overhydrated and also because the distribution of water between the blood volume VS and the interstices has found an equilibrium.

In certain embodiments, the control according to the present invention is contemplated as follows: After 10-30 minutes from the start of the treatment, the direction of the curve is determined (for example, in a representation like the one in Figure 9) . It is evaluated whether or not the curve will probably meet the target range. This assessment can be done by mere observation on the monitor (with the naked eye) or by a more sophisticated approach, such as an algorithm. If the curve is supposed to end within the target range, there is nothing to do. However, if the curve falls too low, as is the case with C2, it may indicate that the blood volume is decreasing too rapidly or too deeply, both indicating that recharge is restricted or limited. Therefore, it would be desirable to limit the IUF ultrafiltration index and prolong the duration of the dialysis treatment. In the end, the curve will be able to reach the target range flat.

On the other hand, in case the curve in Figure 9 extends above the target range, the treatment control can increase the IUF ultrafiltration index until the curve is directed back towards the target range and / or it is believed that reaches the target range or ends in it.

In certain embodiments of the control method or the devices for carrying out the methods, the manipulated variables comprise, first, the ultrafiltration index and / or the duration of the dialysis treatment. In addition, additional means such as salt boluses and their administration are contemplated to enhance recharge.

Figure 10 shows an apparatus 61 comprising a controller 63 configured to carry out the disclosed method. The apparatus 61 is optionally connected to an external database 65 comprising the results of the measurements and the data necessary for the method. The database 65 may also be a means internal to the apparatus 61. The apparatus 61 may optionally have means 67 for inputting data into the controller 63 or into the apparatus 61 itself. Such data may be information on the established ultrafiltration rate, the ultrafiltration volume to be removed from the body, etc., or approximations thereof. The results provided by the controller 63 and / or the apparatus 61 can be displayed on a monitor 60 or represented by a plotter (not displayed in figure 10 but optionally also included) or stored in the database 65 or any other storage medium. The database 65 may also comprise a computer program that initiates the method according to the present invention when it is executed.

As can be seen in Fig. 11, for corresponding measurements, the apparatus 61 according to a second embodiment can be connected (via cables or wirelessly) to a bioimpedance measuring means 69 as an example of a medium. to measure or calculate overhydration, lean mass, fat mass, or other body parameters or approximations thereof. In general, in addition to the external database 65 comprising the measurement results and the data necessary for the method according to the present invention, the means for measurement or calculation can be provided. They can also be provided in place of the external database 65 (ie, as substitutes).

The bioimpedance measuring means 69 can automatically compensate for influences on the impedance data such as contact resistances.

An example of such a bioimpedance measurement means 69 is a device from Xitron Technologies, distributed under the trademark Hydra ™, which is described in more detail in WO 92/19153, the disclosure of which is explicitly incorporated by reference herein this application.

The bioimpedance measurement means 69 may comprise several electrodes. In Figure 7, only two electrodes 69a and 69b are shown which are connected to the bioimpedance measurement means 69. Additional electrodes are of course also contemplated.

Each electrode involved may comprise two or more ("sub-") electrodes in succession. The electrodes may comprise a current injection ("sub-") electrode and a voltage measuring ("sub-") electrode. That is, the electrodes 69a and 69b shown in Figure 11 may comprise two injection electrodes and two voltage measuring electrodes (ie four electrodes in total).

Generally speaking, the apparatus according to the present invention may be provided with means such as weighing means, a keyboard, a touch screen, etc. to enter the required data, sensors, interconnections or communication links with a laboratory, any other means of entry, etc.

Similarly, the apparatus 61 may have other means 71 for measuring or calculating to obtain a value that reflects overhydration and / or to obtain values that reflect the mass, volume, or concentration of Hb that can be provided, in addition to the basis of external data 65 or in place of external database 65 (ie, as surrogates).

The means 71 can be provided as weighing means, a keyboard, touch screen, etc. to enter the required data, sensors, interconnections or communication links with a laboratory, an Hb concentration probe, any other input means, etc.

Next, it is described how an apparatus according to the present invention works which is configured to control a device for treating the blood of a patient, such that the treatment session is finished or interrupted when a threshold or threshold has been detected or calculated. a default value of the patient's absolute blood volume:

The patient's absolute blood volume at the beginning of the treatment session is known as VS_initial = VS_0 + SH / K_Guyton. In the following example, the VS_initial is 5.0L. The relative blood volume determined by, for example, a blood volume monitor several times during treatment is then multiplied by the initial VS_. When the relative blood volume (in%) has dropped to 95%, the absolute blood volume can be calculated as follows: 5.0 l * 0.95 = 4.75 l.

It may be desirable that the blood treatment has to end when the absolute blood volume has fallen below the threshold, for example 4.0 l. In this way, the relative blood volume is taken into account during the blood treatment session. Of course, this threshold can be set individually for each patient and / or treatment session.

Likewise, what has been explained above with respect to the approximation or prediction of a tolerated relative blood volume during blood treatment (see also what has been commented on the method of claim 1) may also be true, in certain embodiments. , for absolute blood volume. In other words, thanks to the present invention it may also be possible to approximate or predict an absolute blood volume that remains tolerable. This final, absolute and tolerated blood volume VS_final can be obtained by multiplying the VS_initial by the VSR_predicted.

Thus, what has been discussed above with respect to the present invention about relative blood volume is also true, in many embodiments, for absolute blood volume.

Claims (13)

1. A blood treatment device for treating a patient by dialysis, comprising at least one controller, configured to control the device based on a computer-implemented method, to calculate a value representing a recharge volume (V recharge) of a patient, which can be observed or found during or due to a blood treatment of the patient, wherein a target range of the relative blood volume (RSV_final) to be achieved by the blood treatment at the end of a treatment session is established as a function of a recharge volume (V recharge) of the patient; where the recharge volume (V recharge) is obtained by the following equation

or V_recharge = a * VUF / Hb + b * SH + c where the relative blood volume (RSV_final) is obtained from the following equation

or by

where: "a", "b", "c", "d" are parameters; Hbjniciai represents the hemoglobin concentration at the beginning of a blood treatment session; Hb is the concentration of hemoglobin; V_recharge represents the recharge volume; VUF represents the ultrafiltration volume; IUF represents the ultrafiltration index; SH represents overhydration of the patient, for example, at the beginning of a blood treatment session; TMJ represents the fat mass of the patient in question; LTM represents the muscle mass of the patient in question; K_Guyton represents the Guyton factor; Y Vs_initial represents the absolute blood volume of the patient at the beginning of the treatment session. 2. A blood treatment apparatus according to claim 1, wherein, to calculate or approximate or predict a value representing the relative blood volume (RSV) or a value representing the recharge volume (V recharge), it is considered the absolute initial blood volume (VS_initial) at the beginning of or before blood treatment. A blood treatment apparatus according to claim 2, wherein, to evaluate the absolute initial blood volume (VS_initial), at least one value reflecting the lean mass (LTM) and at least one value reflecting the lean mass (LTM) are considered fat mass (TMJ) of the patient's body, or approximations of these. 4. A blood treatment device according to any of the preceding claims, the method encompassing the step: - predicting a final value of the relative blood volume (RSV) which is reached at the end of a blood treatment session without having caused intradialysis pathological complications, such as hypotonic episodes and the like. 5. A blood treatment device according to any one of the preceding claims, wherein a blood treatment apparatus is controlled as a function of the relative blood volume (RSV) obtained from the method set forth in any one of claims 1-3, or as a function of a final value of the relative blood volume (RSV) obtained from the method set forth in claim 4. 6. A blood treatment device according to any one of the preceding claims, wherein the time that a certain future blood treatment session lasts is calculated or optimized taking into account the relative blood volume (RSV) obtained from the stated method in any of claims 1-3, or the final value of the relative blood volume (RSV) obtained from the method set forth in claim 4. A blood treatment device according to any one of the preceding claims, the apparatus further comprising an output device for outputting the results provided in carrying out the respective method. A blood treatment device according to any preceding claim, the apparatus being configured to control a device for treating a patient's blood with respect to a target value or range representing the relative blood volume (RSV) or the normalized or normohydrated blood volume (RSV_normohid), calculated or approximated or predicted by a method as set forth in any of claims 1 to 7. A blood treatment device according to any preceding claim, the apparatus being configured to control a device for treating a patient's blood with respect to a target value or range representing the target relative blood volume (RSV), calculated by a method as set forth in any one of claims 1 to 8, wherein the target range is further defined by a target overhydration state. A blood treatment device according to any of the preceding claims, the apparatus being configured to control a device for treating a patient's blood so that the treatment session is over or interrupted once it is measured or calculated. a final value of the relative blood volume (RSV) that has been predicted as a final value or target range of the relative blood volume (RSV) with which the patient has not suffered intradialytic pathological complications, such as hypotonic episodes and others. A blood treatment device according to any one of the preceding claims, the apparatus being configured to control a device for treating a patient's blood so that the treatment session is over or interrupted once it has been detected or calculated a threshold or a predetermined value of the patient's absolute blood volume. A blood treatment device according to any of the preceding claims, the apparatus being configured to control a device for treating a patient's blood so that the treatment session is over or interrupted once it has been detected or calculated a threshold or a predetermined value of the patient's absolute blood volume, wherein the patient's absolute blood volume is determined during the blood treatment session taking into account the relative blood volume determined during the blood treatment session. A blood treatment device according to any of the preceding claims, the device being configured to treat a patient by hemofiltration, ultrafiltration and / or hemodialysis.